Using S tem Cells to Make Pancreatic Organoids

Large scale generation of functional and vascularized pancreaticorgan-like s tructures from human s tem cells will facilitate understanding human pancreas developmental biology. Achievingto such an in vitro tool could also be a useful for drug-screeningor therapeutic applications for diabetes. However, mechanicaland chemical properties of microenvironment, cell types andratios are important parameters that pose challenges in productionof functional pancreatic organoids. Furthermore, organoidformation process and further differentiation in vivo can becompletely different from in vitro. During the earlies t s tage ofpancreas organogenesis, the pancreatic epithelium evaginatesinto the surrounding non-epithelial niche; Cellular componentsof the niche secret different growth factors for pancreatic progenitor’s(PP) expansion and subsequent differentiation.Therefore, for the las t decade, we have s tudied combinations ofdifferent s tem cells with human pluripotent s tem cell derived pancreaticprogenitors. We inves tigated the effect of supportive cellsas well as different culture conditions in formation of functionalpancreatic organoids. During these s tudies, we developed PP differentiationprotocols and co-culture sys tem to s tudy the effectsof hESC derived mesenchymal s tem cells (MSC), endothelialcells as well as human fetal pancreas mesenchymal cells (hFPMCs)and bone marrow derived MSC on pancreatic organoids/spheroids formation. Produced s tructures were also evaluated invitro and in vivo for different functional parameters.We found that cell density/type/ratio are important parameterin self-organization process and organoid formation and wereported that niche-specific s tem cells (hFP-MCs) can facilitatefurther differentiation of PP through a scalable co-culturesys tem. These findings can help developing pancreatic/isletlikeorganoids for diabetes cell replacement therapies and drugdiscovery.

کلیدواژه ها:

Embryonic S tem Cells ، Organoids ، Pancreatic Differentiation ، Pancreatic Fetal Mesenchyme ، Pancreatic Progenitor